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Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile.

Abstract：

AIM:Nowadays, extracellular vesicles are of great interest in prostate cancer (PCa) research. Asparagine (N)-linked glycosylation could play a significant role in the pathological mechanism of these vesicles. We investigated if prostatic protein N-glycosylation profiles were related to urinary vesicle-associated prostate-specific antigen (PSA) extractability and if this parameter showed diagnostic potential for PCa. METHODS:Urinary extracellular vesicles were visualised using transmission electron microscopy. Urinary extracellular vesicles extraction by means of n-butanol allowed determination of urinary vesicle-associated PSA extractability. Diagnostic value was assessed between benign prostate hyperplasia (BPH; n=122) and patients with PCa (n=85). Additionally, correlation with urine N-glycosylation was assessed. RESULTS:Urinary extracellular vesicles with a diameter of approximately 100 nm were more abundantly present in urine of patients with PCa versus patients with BPH resulting in a higher vesicle-associated PSA extraction ratio (p<0.001). Next, vesicle-associated PSA extraction ratio was correlated to biantennary core-fucosylation (p=0.003). Finally, vesicle-associated PSA extraction ratio proved beneficial in PCa diagnosis, next to serum PSA and the urinary glycosylation marker (p=0.021). CONCLUSIONS:The urinary vesicle-associated PSA extraction ratio is increased in PCa which is a direct result of the abundant presence of extracellular vesicles in urine of patients with PCa. The urinary vesicle-associated PSA extraction ratio was associated with changes in N-glycoforms and showed diagnostic potential. Further research is warranted to unravel the pathological link between N-glycosylation and extracellular vesicles in cancer, as well as to assess the prognostic value of this biomarker.

journal_name

J Clin Pathol

journal_title

Journal of clinical pathology

authors

Vermassen T,D'Herde K,Jacobus D,Van Praet C,Poelaert F,Lumen N,Callewaert N,Decaestecker K,Villeirs G,Hoebeke P,Van Belle S,Rottey S,Delanghe J

doi

10.1136/jclinpath-2016-204312

subject

Has Abstract

pub_date

2017-10-01 00:00:00

pages

838-846

issue

eissn

0021-9746

issn

1472-4146

pii

jclinpath-2016-204312

journal_volume

pub_type

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Release of urinary extracellular vesicles in prostate cancer is associated with altered urinary N-glycosylation profile.